The research project seeks to define the molecular basis of Rh antigenicity in the human erythrocyte plasma membrane. Use of radiolabeled antibody and membrane biochemical techniques has tentatively identified the macromolecular structure of this lipid-dependent membrane protein antigen. Three polypeptides appear to be associated with Rho(D) activity, including possibly the major red cell membrane polypeptide (band 3). It is proposed to study the role of these components in Rh function as well as the nature of the membrane lesion or deletion in Rh-null cells. The physico-chemical basis for the role of phospholipids and cholesterol in Rh activity will be investigated. Immunoelectron microscopy of isolated Rh in model lipid membranes will further our understanding of antibody-mediated antigenic redistribution and membrane dynamics. The elucidation of the molecular biology of Rh will further our understanding of this clinically-important blood group and of biological membranes in general.